APOE -ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals
(2023) In EJNMMI Research 13(1).- Abstract
Purpose: To determine whether the APOE-ε4 allele modulates the relationship between regional β-amyloid (Aβ) accumulation and cognitive change in middle-aged cognitively unimpaired (CU) participants. Methods: The 352 CU participants (mean aged 61.1 [4.7] years) included completed two cognitive assessments (average interval 3.34 years), underwent [18F]flutemetamol Aβ positron emission tomography (PET), T1w magnetic resonance imaging (MRI), as well as APOE genotyping. Global and regional Aβ PET positivity was assessed across five regions-of-interest by visual reading (VR) and regional Centiloids. Linear regression models were developed to examine the interaction between regional and global Aβ PET positivity and APOE-ε4 status on... (More)
Purpose: To determine whether the APOE-ε4 allele modulates the relationship between regional β-amyloid (Aβ) accumulation and cognitive change in middle-aged cognitively unimpaired (CU) participants. Methods: The 352 CU participants (mean aged 61.1 [4.7] years) included completed two cognitive assessments (average interval 3.34 years), underwent [18F]flutemetamol Aβ positron emission tomography (PET), T1w magnetic resonance imaging (MRI), as well as APOE genotyping. Global and regional Aβ PET positivity was assessed across five regions-of-interest by visual reading (VR) and regional Centiloids. Linear regression models were developed to examine the interaction between regional and global Aβ PET positivity and APOE-ε4 status on longitudinal cognitive change assessed with the Preclinical Alzheimer’s Cognitive Composite (PACC), episodic memory, and executive function, after controlling for age, sex, education, cognitive baseline scores, and hippocampal volume. Results: In total, 57 participants (16.2%) were VR+ of whom 41 (71.9%) were APOE-ε4 carriers. No significant APOE-ε4*global Aβ PET interactions were associated with cognitive change for any cognitive test. However, APOE-ε4 carriers who were VR+ in temporal areas (n = 19 [9.81%], p = 0.04) and in the striatum (n = 8 [4.14%], p = 0.01) exhibited a higher decline in the PACC. The temporal areas findings were replicated when regional PET positivity was determined with Centiloid values. Regionally, VR+ in the striatum was associated with higher memory decline. As for executive function, interactions between APOE-ε4 and regional VR+ were found in temporal and parietal regions, and in the striatum. Conclusion: CU APOE-ε4 carriers with a positive Aβ PET VR in regions known to accumulate amyloid at later stages of the Alzheimer’s disease (AD) continuum exhibited a steeper cognitive decline. This work supports the contention that regional VR of Aβ PET might convey prognostic information about future cognitive decline in individuals at higher risk of developing AD. ClinicalTrials.gov Identifier: NCT02485730. Registered 20 June 2015 https://clinicaltrials.gov/ct2/show/NCT02485730 and ClinicalTrials.gov Identifier:NCT02685969. Registered 19 February 2016 https://clinicaltrials.gov/ct2/show/NCT02685969.
(Less)
- author
- author collaboration
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer’s disease, Amyloid PET, APOE-ε4, Executive function, Memory, Visual read
- in
- EJNMMI Research
- volume
- 13
- issue
- 1
- article number
- 18
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:36856866
- scopus:85149394010
- ISSN
- 2191-219X
- DOI
- 10.1186/s13550-023-00967-6
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2023, The Author(s).
- id
- ea1185a4-af23-429b-bf82-28e93942b49f
- date added to LUP
- 2024-01-12 14:13:49
- date last changed
- 2024-04-27 09:35:37
@article{ea1185a4-af23-429b-bf82-28e93942b49f,
abstract = {{<p>Purpose: To determine whether the APOE-ε4 allele modulates the relationship between regional β-amyloid (Aβ) accumulation and cognitive change in middle-aged cognitively unimpaired (CU) participants. Methods: The 352 CU participants (mean aged 61.1 [4.7] years) included completed two cognitive assessments (average interval 3.34 years), underwent [<sup>18</sup>F]flutemetamol Aβ positron emission tomography (PET), T1w magnetic resonance imaging (MRI), as well as APOE genotyping. Global and regional Aβ PET positivity was assessed across five regions-of-interest by visual reading (VR) and regional Centiloids. Linear regression models were developed to examine the interaction between regional and global Aβ PET positivity and APOE-ε4 status on longitudinal cognitive change assessed with the Preclinical Alzheimer’s Cognitive Composite (PACC), episodic memory, and executive function, after controlling for age, sex, education, cognitive baseline scores, and hippocampal volume. Results: In total, 57 participants (16.2%) were VR+ of whom 41 (71.9%) were APOE-ε4 carriers. No significant APOE-ε4*global Aβ PET interactions were associated with cognitive change for any cognitive test. However, APOE-ε4 carriers who were VR+ in temporal areas (n = 19 [9.81%], p = 0.04) and in the striatum (n = 8 [4.14%], p = 0.01) exhibited a higher decline in the PACC. The temporal areas findings were replicated when regional PET positivity was determined with Centiloid values. Regionally, VR+ in the striatum was associated with higher memory decline. As for executive function, interactions between APOE-ε4 and regional VR+ were found in temporal and parietal regions, and in the striatum. Conclusion: CU APOE-ε4 carriers with a positive Aβ PET VR in regions known to accumulate amyloid at later stages of the Alzheimer’s disease (AD) continuum exhibited a steeper cognitive decline. This work supports the contention that regional VR of Aβ PET might convey prognostic information about future cognitive decline in individuals at higher risk of developing AD. ClinicalTrials.gov Identifier: NCT02485730. Registered 20 June 2015 https://clinicaltrials.gov/ct2/show/NCT02485730 and ClinicalTrials.gov Identifier:NCT02685969. Registered 19 February 2016 https://clinicaltrials.gov/ct2/show/NCT02685969.</p>}},
author = {{Brugulat-Serrat, Anna and Sánchez-Benavides, Gonzalo and Cacciaglia, Raffaele and Salvadó, Gemma and Shekari, Mahnaz and Collij, Lyduine E. and Buckley, Christopher and van Berckel, Bart N.M. and Perissinotti, Andrés and Niñerola-Baizán, Aida and Milà-Alomà, Marta and Vilor-Tejedor, Natàlia and Operto, Grégory and Falcon, Carles and Grau-Rivera, Oriol and Arenaza-Urquijo, Eider M. and Minguillón, Carolina and Fauria, Karine and Molinuevo, José Luis and Suárez-Calvet, Marc and Gispert, Juan Domingo and Cañas, Alba and Canals, Lidia and Iglesias, Laura and Marne, Paula and Beteta, Annabella and Deulofeu, Carme and Emilio, Maria and Cumplido, Irene and Domínguez, Ruth and Fuentes, Sherezade and Hernández, Laura and Vilanova, Marc and Solsona, Lluís and Huesa, Gema and Huguet, Jordi and Menchón, Tania and Polo, Albina and Pradas, Sandra and Sala-Vila, Aleix and Soteras, Anna and Stankeviciute, Laura and Akinci, Müge and Palpatzis, Eleni and Genius, Patricia and Rodríguez, Blanca and García, Marina and Ortiz-Romero, Paula}},
issn = {{2191-219X}},
keywords = {{Alzheimer’s disease; Amyloid PET; APOE-ε4; Executive function; Memory; Visual read}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{EJNMMI Research}},
title = {{APOE -ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals}},
url = {{http://dx.doi.org/10.1186/s13550-023-00967-6}},
doi = {{10.1186/s13550-023-00967-6}},
volume = {{13}},
year = {{2023}},
}